PROJECT SUMMARY Overview: Over 60% of myeloid neoplasms (MN) are diagnosed in adults aged ?60 years, and up to 98% of these patients [including those receiving hypomethylating agents (HMA)] experience physical function decline and symptoms (e.g. fatigue, mood disturbances), leading to poor quality of life (QoL). Exercise may prevent physical function decline and improve symptoms in older patients with MN. Older patients with MN can exercise safely, but adherence may be a challenge. Mobile health (mHealth) application (app) may improve adherence by enhancing exercise self-efficacy and by helping to address barriers to exercise. Inflammatory dysregulation [specifically tumor necrosis factor (TNF)? and related cytokines] is associated with physical function decline, fatigue, and mood disturbances. In this K99/R00, we propose to develop, adapt, and evaluate a novel mHealth exercise intervention for preventing physical function decline, improving symptoms, and preventing worsening QoL in older patients with MN receiving outpatient HMA, and to explore the effect of the intervention on TNF? and related cytokine gene promoter methylation and their gene and protein expression. Career Development Plan: Dr. Loh is an emerging geriatric oncologist and has begun to study mHealth and cancer control. To become an independent clinician scientist conducting mHealth behavioral intervention research for older patients with MN, Dr. Loh needs training to (1) develop and adapt mHealth behavioral interventions for older patients with cancer, (2) acquire skills to become an independent investigator who can design, conduct, and analyze clinical trials, (3) develop expertise in biomarkers of physical function. Dr. Loh's mentoring team has expertise in geriatric and exercise oncology, behavioral intervention research, mHealth, and translational science. The University of Rochester is world-class for geriatric oncology and cancer control. Research Plan: The proposed mHealth exercise intervention (GO-EXCAP Mobile App) integrates the content of an established exercise program (EXCAP) with a mobile app delivery platform (TouchStream). EXCAP is a home-based progressive walking and resistance exercise program. The TouchStream mobile app tracks exercise data, symptoms, and barriers to exercise adherence, and the exercise physiologist can adjust exercise prescriptions and address barriers to exercise. In K99, we will first develop and adapt the GO-EXCAP Mobile App by obtaining feedback from 10 patients with MN receiving HMA. Second, we will conduct a single- arm phase 1 trial to optimize the GO-EXCAP Mobile App in 25 patients. In R00 (phase 2 randomized controlled trial), we will assess the preliminary efficacy of the GO-EXCAP Mobile App versus a chemotherapy education control (behavioral placebo) on physical function and patient-reported outcomes (fatigue, mood, and QoL) in 100 patients. We will also explore the effect of the intervention on TNF? and related cytokine pathways. Impact: The combined training and research plan will position Dr. Loh to become one of the few geriatric oncology investigators studying mHealth interventions, and to allow her to transition to independence.